Serum Vitamin K1 Research Articles

The association of serum vitamin K2 levels with Parkinson's disease: from basic case-control study to big data mining analysis

Although it is known that inflammation is involved in Parkinson’s disease (PD) pathogenesis and vitamin K2 (VK2) has anti-inflammatory effects, to date few studies have been reported on the relationship between VK2 and PD development. Herein we presented a case-control study involving 93 PD patients and 95 healthy controls. Overall, the serum VK2 level of PD patients (3.49 ± 1.68 ng/ml) was significantly lower than that of healthy controls (5.77 ± 2.71 ng/ml). When the PD patients were stratified by disease progression, we observed that the serum VK2 level of late stage patients was further decreased to 3.15 ± 1.18 ng/ml while the serum VK2 level of early stage patients was 3.92 ± 2.09 ng/ml. Furthermore, the curve analysis showed that the serum VK2 level decreased gradually with the increment of PD Hoehn-Yahr (H-Y) stage. We also confirmed the dysregulated inflammatory responses and coagulation cascades in PD patients by public dataset, which are associated to the decreased VK2 level. In summary, we found the serum VK2 level in PD patients is lower than that in healthy controls. The decrease of VK2 level may be related to the occurrence and progression of PD by loosening the regulation of inflammatory responses and coagulation cascades signal.

In Search of Normality for Vitamin K1: Establishing Age-Dependent Reference Intervals in the Danish Population.

A growing body of evidence suggests that vitamin K has beneficial effects on human health, especially cardiovascular and bone health. Vitamin K1 (phylloquinone), the predominant form of vitamin K in blood, is regarded as an indicator of vitamin K status, but to our knowledge no reference intervals (RIs) have been established for vitamin K1. In this population-based study, vitamin K1 was measured in serum from 3808 Caucasian individuals without diabetes from 26 to 78 years of age. The need for gender- and age-partitioned vitamin K1 reference intervals was evaluated using Lahti's method, and exclusion criteria were defined to obtain as healthy a study group as possible. The excluded subgroups were tested for differences in mean serum vitamin K1 levels. Serum vitamin K1 levels were quantified using an in-house newly developed, validated, and highly sensitive online SPE-LC-MS/MS method with a limit of quantitation of (LOQ) 0.05 nmol/L. The reference interval for serum vitamin K1 was 0.22 to 3.95 nmol/L for individuals aged 26 to 44 years and 0.35 to 3.70 nmol/L for individuals aged 45 to 78. Similar age-specific reference intervals were established for vitamin K1-triglyceride ratio being 0.20 to 3.16 and 0.31 to 3.44, respectively. No significant difference was found between genders. Serum vitamin K1 was detectable in all serum samples. Individuals with known comorbidity were found to have significantly lower serum vitamin K1 compared to those without comorbidity. Current smokers had lower serum vitamin K1 compared to nonsmokers. Age-dependent reference intervals were established for serum vitamin K1 and vitamin K1-triglyceride ratio in a well-defined, healthy Caucasian population. Lower serum vitamin K1 levels were found in individuals with known comorbidity, suggesting an association between serum vitamin K1 and disease status. Further studies are needed to determine an optimal serum vitamin K1 level.

Serum vitamin K1 associated to microangiopathy and/or macroangiopathy in individuals with and without diabetes

ObjectiveVitamin K has proposed beneficial effects on cardiovascular health. We investigated whether serum vitamin K1 was associated with prevalence of microangiopathy and/or macroangiopathy.Research design and methodsSerum vitamin K was quantified...

Fruit and Vegetable Treatment of Chronic Kidney Disease-Related Metabolic Acidosis Reduces Cardiovascular Risk Better than Sodium Bicarbonate

Background: Current guidelines recommend treatment of metabolic acidosis in chronic kidney disease (CKD) with sodium-based alkali. We tested the hypothesis that treatment with base-producing fruits and vegetables (F + V) better improves cardiovascular disease (CVD) risk indicators than oral sodium bicarbonate (NaHCO₃). Methods: We randomized 108 macroalbuminuric, matched, nondiabetic CKD patients with metabolic acidosis to F + V (n = 36) in amounts to reduce dietary acid by half, oral NaHCO₃ (HCO₃, n = 36) 0.3 mEq/kg bw/day, or to Usual Care (UC, n = 36) to assess the 5-year effect of these interventions on estimated glomerular filtration rate (eGFR) course as the primary analysis and on indicators of CVD risk as the secondary analysis. Results: Five-year plasma total CO₂ was higher in HCO₃ and F + V than UC but was not different between HCO₃ and F + V (difference p value < 0.01). Five-year net eGFR decrease was less in HCO₃ (mean –12.3, 95% CI –12.9 to –11.7 mL/min/1.73 m²) and F + V (–10.0, 95% CI –10.6 to –9.4 mL/min/1.73 m²) than UC (–18.8, 95% CI –19.5 to –18.2 mL/min/1.73 m²; p value < 0.01) but was not different between HCO₃ and F + V. Five-year systolic blood pressure was lower in F + V than UC and HCO₃ (p value < 0.01). Despite similar baseline values, F + V had lower low-density lipoprotein, Lp(a), and higher serum vitamin K1 (low serum K1 is associated with coronary artery calcification) than HCO₃ and UC at 5 years. Conclusion: Metabolic acidosis improvement and eGFR preservation were comparable in CKD patients treated with F + V or oral NaHCO₃ but F + V better improved CVD risk indicators, making it a potentially better treatment option for reducing CVD risk.

Quantitation of vitamin K1 in serum using online SPE-LC-MS/MS and the challenges of working with vitamin K

Vitamin K1 (phylloquinone) is one of the vitamin Ks. Several studies have previously investigated the role of vitamin K1 status in respect to disease, but without consistent results. Since vitamin K deficiency has been associated with different disease states it is important to develop a biochemical analysis with sufficient sensitivity and a low limit of quantitation (LOQ).The vitamin Ks are very fat-soluble. This non-polar nature has given rise to several challenges during the method development, because vitamin K1 sticks to materials used during the process and is lost during evaporation. We found that reducing the sample preparation as much as possible offline, instead using online SPE-LC-MS/MS improves recovery and gives satisfactory chromatograms. An Protein BEH C4 column, 300 Å (50 × 2.1 mm, 1.7 μm particle size) was used as trap column and a Phenyl-Hexyl-LC-column, 100 Å (100 × 2.1 mm, 2.6 μm particle size) was used as analytical column. The mobile phases consisted of 30 μmol/L NH4F in water and 30 μmol/L NH4F in MeOH. A triple quadrupole tandem mass spectrometer with atmospheric pressure chemical ionization (APCI) ion source, positive ion mode, was used to perform the mass spectrometric measurements.The method is simple, highly sensitive and fast. The method was validated for vitamin K1 with good analytical performance. With a LOQ of 0.05 nmol/L it is to our knowledge the vitamin K1 method with lowest LOQ reported to date in the literature. It can easily be automated and applied in a routine diagnostic laboratory.Blood collection tubes with different additives were tested and showed no difference. Stability of vitamin K1 in serum was tested at different temperatures (−20 °C, 4 °C and in light and dark at 20 °C over a period of 30 days) and showed that vitamin K1 is light sensitive in serum even after only one day.

Alterations of serum vitamin K levels and prothrombin time-international normalized ratio during tooth extractions among patients receiving warfarin

ObjectiveThe British guideline described that antibiotic treatment during tooth extraction kills bacteria in the intestine, which reduces their production of vitamin K and leads to an increased prothrombin time-international normalized ratio (PT-INR). In this study, we attempted to clarify the influence of antibiotics on serum vitamin K levels and alteration of PT-INR in patients receiving warfarin. MethodsWe measured PT-INR and serum vitamin K levels (K1 from diet and K2 from intestinal bacteria) among 11 patients receiving warfarin during tooth extractions (on days 0, 1, 3, and 5) at Dokkyo Medical University Hospital, Sano Kosei General Hospital and Kamma Memorial Hospital from 2008 to 2018. All patients received 5 days of oral antibiotic treatment after the tooth extractions. ResultsThere were no significant changes in PT-INR between days 0 and 5. Serum vitamin K1 levels on day 0 were varied. Most patients had decreased serum vitamin K1 levels on days 1 and 3. Mean serum vitamin K1 levels on day 3 were significantly lower than those on day 0 (p = 0.04) in patients who were admitted to Dokkyo Medical University Hospital. Most patients still had low serum vitamin K1 levels between days 3 and 5. Serum vitamin K2 levels in most patients examined were below the detection limit (0.05 ng/ml) except two patients (0.24 ng/ml, 0.06 ng/ml at day 0). ConclusionIt appears that antibiotic treatment during tooth extractions might not affect PT-INR among patients receiving warfarin through the alteration of serum vitamin K2 production by intestinal bacteria.

Impact of Vitamin K1on Tissue Vitamin K Levels, Immunity, and Survival of Greenlip Abalone,Haliotis laevigata, at Summer Water Temperatures

Summer mortality impacts the productivity of greenlip abalone, Haliotis laevigata, on land-based farms in South Australia. It is associated with high water temperature (greater than 23°C), low dissolved oxygen levels, increased bacterial loads, and immune system suppression during summer months. This study aimed to alleviate mortality rates of greenlip abalone by dietary intervention using vitamin K1 to support the innate immune system and oxidative status. Dietary vitamin K1 at 0.0, 0.5, 1.0, and 5.0 mg kg-1 was added to a commercially formulated diet mash. An additional diet containing 0.5 mg kg-1 of K3 was also used for comparison. Diets were fed to 3-y-old abalone (71.51 g; 79.91 mm) at 22 and 25°C water temperatures for 39 days. No mortalities were observed at 22°C; however, high mortalities were observed in all dietary treatments at the water temperature of 25°C. Compared with the negative control diet (0.0 mg additional inclusion ofK1 or K3 kg-1) at 25°C, the inclusion of vitaminK1 orK3 did not improve survival of greenlip abalone (P > 0.05). VitaminK1 inclusion level resulted in significant increases in vitamin K1 concentration of visceral organ and muscle tissues (P 0.05). Increasing water temperature to 25°C resulted in significant increases in serum catalase activity (22 K3) and vitamin K1 concentration in visceral organ (K1 >K3). In conclusion, vitaminK1 at the doses tested, resulted in significant increases in vitaminK1 concentration in visceral organ and muscle tissues, but failed to improve immune function, oxidative status, or survival of greenlip abalone at high summer water temperatures.

Relation Between Circulating Vitamin K1 and Osteoporosis in the Lumbar Spine in Syrian Post-Menopausal Women.

Background:In the past two decades, Vitamin K has been receiving more attention due to its role in bone health and metabolism. The bone mineral density does not remain steady with age, particularly declining after menopause.Objective: This study is aimed to investigate the relationship between bone mineral density and serum vitamin K1 levels in post-menopausal women, and to evaluate serum vitamin K1 levels as a potential biomarker for postmenopausal osteoporosis.Methods:Serum levels of vitamin k1 were measured in 23 postmenopausal osteoporotic women, and in 15 postmenopausal healthy control women using a standardized Enzyme-Linked Immune Sorbent Assay (ELISA) kit. Bone mineral density BMD was assessed at the lumbar spine.Results:The mean serum vitamin k1 level was significantly lower in the postmenopausal osteoporotic women group than in the normal control group (mean=0.794 vs3.61ng/ml, P< 0.0001), and serum vitamin k1 concentration was positively correlated with lumbar spine BMD among postmenopausal osteoporotic women (R=0.533, p = 0.009), and in postmenopausal healthy control (R=0.563, p = 0.02).Diagnostic sensitivity and specificity of vitamin k1 for osteoporosis were 90% and 98%, respectively (cut-off value: 0.853 ng/ml). The area under the ROC curve (AUC) value for vitamin k1 was 0.984 the odd ratio result was 18.66.Conclusion:Our results suggest that vitamin K1 may contribute to maintain bone mineral density. Vitamin K1 may have a role in diagnosing post-menopausal osteoporosis. Vitamin K1 may be a valuable diagnostic as well as therapeutic marker in post-menopausal osteoporosis.

Routine Supercritical Fluid Chromatography Tandem Mass Spectrometry Method for Determination of Vitamin K1 Extracted from Serum with a 96-Well Solid-Phase Extraction Method.

The concentration of vitamin K1 in serum or plasma is the most common index for assessing vitamin K status. The aim of this study was to develop and validate a rapid and reliable routine method for quantifying vitamin K1 above 0.1 ng/mL. Semi-automation of a simple sample preparation with fast analysis by supercritical fluid chromatography-tandem mass spectrometry (SFC-MS/MS) was exploited. Vitamin K1 was extracted from 250-μL serum samples by the use of protein precipitation and reversed-phase solid-phase extraction (SPE) in 96-well plates and quantified by SFC on a 2.1 × 100 mm Torus 1-Aminoanthracene (1-AA) column in 3.8 min with electrospray ionization-tandem mass spectrometry (MS/MS) detection. This method shows good linearity in the concentration range of 0.1-50 ng/mL with a correlation coefficient of R2 >0.999. Imprecision was satisfactory, with repeatability and reproducibility <10% CV. The lower limit of the measuring interval was 0.1 ng/mL, and no systematic bias was observed for the method, which used vitamin K1-d7 as internal standard. Recovery of vitamin K1 in external quality controls was satisfactory compared to other laboratories participating in the external quality assurance scheme. The method is currently in routine use for analysis of serum samples. The method allows high-throughput reliable determination of vitamin K1 in serum in the range 0.1-50 ng/mL.

Determination of vitamin K1 in blood serum by high-performance liquid chromatography

A method is proposed for the determination of vitamin K1 concentration in blood serum using HPLC on a Gemini C18 (250 mm × 4.6 mm ID, 5 μm) column and elution with a methanol–acetonitrile–dichloromethane (45 : 50 : 5, v/v) mobile phase at a flow rate of 1 mL/min and detection at 248 nm. The limit of detection for the vitamin is 0.5 ng/mL and relative error is 19%. The volume of sample in the column is 100 μL. The method has been applied to the evaluation of vitamin K1 deficit in a human body in medical practice.

A combination of low serum concentrations of vitamins K1 and D is associated with increased risk of hip fractures in elderly Norwegians: a NOREPOS study.

The present study investigated the risk of incident hip fractures according to serum concentrations of vitamin K1 and 25-hydroxyvitamin D in elderly Norwegians during long-term follow-up. The results showed that the combination of low concentrations of both vitamin D and K1 provides a significant risk factor for hip fractures. This case-cohort study aims to investigate the associations between serum vitamin K1 and hip fracture and the possible effect of 25-hydroxyvitamin D (25(OH)D) on this association. The source cohort was 21,774 men and women aged 65 to 79years who attended Norwegian community-based health studies during 1994-2001. Hip fractures were identified through hospital registers during median follow-up of 8.2years. Vitamins were determined in serum obtained at baseline in all hip fracture cases (n = 1090) and in a randomly selected subcohort (n = 1318). Cox proportional hazards regression with quartiles of serum vitamin K1 as explanatory variable was performed. Analyses were further performed with the following four groups as explanatory variable: I: vitamin K1 ≥ 0.76 and 25(OH)D ≥ 50nmol/l, II: vitamin K1 ≥ 0.76 and 25(OH)D < 50nmol/l, III: vitamin K1 < 0.76 and 25(OH)D ≥ 50nmol/l, and IV: vitamin K1 < 0.76 and 25(OH)D < 50nmol/l. Age- and sex-adjusted analyses revealed an inverse association between quartiles of vitamin K1 and the risk of hip fracture. Further, a 50% higher risk of hip fracture was observed in subjects with both low vitamin K1 and 25(OH)D compared with subjects with high vitamin K1 and 25(OH)D (HR 1.50, 95% CI 1.18-1.90). The association remained statistically significant after adjusting for body mass index, smoking, triglycerides, and serum α-tocopherol. No increased risk was observed in the groups low in one vitamin only. Combination of low concentrations of vitamin K1 and 25(OH)D is associated with increased risk of hip fractures.

Management of vitamin K deficiency after biliopancreatic diversion with or without duodenal switch

BackgroundReduced serum vitamin K levels are frequently observed after biliopancreatic diversion (BPD) and BPD with duodenal switch (BPD/DS). The criteria for treatment are not precisely defined. ObjectivesTo assess the effects of standardized vitamin K supplementation in patients who develop vitamin K deficiency after BPD or BPD/DS. SettingTeaching hospital specializing in bariatric surgery. MethodsSerum vitamin K levels, clotting times, and vitamin K-dependent coagulation factors were measured after an overnight fast at baseline and then at 4 days and 1, 4, and 52 weeks after the start of vitamin K supplementation in 10 consecutive patients who had developed severe vitamin K deficiency after BPD or BPD/DS. Vitamin K was administered in a dose of 5 mg/d for 1 week, followed by a maintenance dose of 5 mg once a week. ResultsAt baseline, all patients had serum vitamin K1 levels below the limit of detection, but none reported symptoms of easy bleeding. Minor prolongation of the prothrombin time and minimal decreases of some coagulation factors were observed in a minority of patients. During the first week of vitamin K loading, median serum vitamin K1 levels rose into the high normal range. During maintenance treatment, median vitamin K1 levels settled in the low normal range. ConclusionVitamin K1 deficiency in patients with BPD or BPD/DS is not commonly associated with bleeding or clinically relevant decreases in coagulation factor activity. We hypothesize that vitamin K2 production in the large intestine is usually sufficient to compensate for vitamin K1 deficiency and to maintain total liver vitamin K stores within the range required for (near) normal coagulation factor production.

O-042: Low serum vitamin K1 increases the risk of hip fractures only at low vitamin D status. A NOREPOS study

O-042: Low serum vitamin K1 increases the risk of hip fractures only at low vitamin D status. A NOREPOS study

Two novel HTRA1 mutations in a European CARASIL patient

Two patients with low random serum vitamin K1 concentrations but with normal prothrombin times and normal biological assays of the vitamin K dependent coagulation proteins were treated with an N-methyl-thiotetrazole cephalosporin (cefotetan) postoperatively. Four to six days later both patients developed a prolonged prothrombin time and a noticeable and specific lowering of the clotting activities of factors II, VII, IX and X, though the serum vitamin K1 concentrations remained unchanged. Crossed immunoelectrophoresis of prothrombin showed the appearance of a second peak corresponding to descarboxyprothrombin (PIVKA II). These abnormalities corrected after vitamin K administration. These data are consistent with the hypothesis that cephalosporins with an N-methyl-thiotetrazole side chain inhibit the hepatic utilisation of vitamin K but that this only causes hypoprothrombinaemia when liver reserves of vitamin K are low.

Impact of Supplemental Vitamin K1 Administration on Postoperative Blood Component Requirements After Craniosynostosis Repair

Total cranial vault craniosynostosis repairs often require additional blood transfusions in the intensive care unit. Vitamin K1 participates in hepatic production of procoagulant proteins, and body stores of vitamin K1 are limited and dietary dependent. Surgical stress and diet interference may place infants at risk for vitamin K deficiency. Through design of a surgically stratified, randomized, placebo-controlled, blinded pilot study, we evaluated impact of vitamin K1 supplementation on coagulation parameters in infants after craniosynostosis repair. Patients received intramuscular vitamin K1 or placebo coincident with surgical incision. Serum vitamin K1 levels, protein induced in vitamin K absence-prothrombin, and factor VII were obtained at predetermined intervals after surgery. Patients received blood products in the intensive care unit in accordance with transfusion thresholds. Fifteen patients (vitamin K1 = 6, placebo = 9) completed the study procedures. Despite group assignment, patients received an average of 3 postoperative transfusions. Variations were observed with respect to intraoperative resuscitation of patients between comparably trained pediatric anesthesiologists. Thirty-three percent of patients were vitamin K1 deficient on 1 or more laboratory specimens. All breast-fed patients became deficient. Compared with placebo, elevated serum vitamin K1 levels at 6, 12, and 24 hours in the active drug group (P < 0.0001) were not associated with increased factor VII levels or reduced need for postoperative blood products. However, lack of a standardized intraoperative resuscitation plan may contribute to postoperative coagulopathy and is a major study limitation.

Association between circulating vitamin K1 and coronary calcium progression in community-dwelling adults: the Multi-Ethnic Study of Atherosclerosis

Animal studies have shown that vitamin K treatment reduced vascular calcification, but human data are limited. We determined the association between vitamin K status and coronary artery calcium (CAC) progression in the Multi-Ethnic Study of Atherosclerosis by using a case-cohort design. Serum phylloquinone (vitamin K1) was measured in 296 participants with extreme CAC progression and 561 randomly selected participants without extreme CAC progression; all subjects had baseline and follow-up CAC measures (mean follow-up: 2.5 y). A serum vitamin K1 concentration was considered low at <1.0 nmol/L (the distribution median). Outcomes were replicated by using post hoc per-protocol analyses of a vitamin K1 supplementation trial. The OR (95% CI) for extreme CAC progression for subjects with low serum vitamin K1 compared with subjects without extreme CAC progression was 1.34 (0.94, 1.90; NS) when adjusted for demographics and confounders. A significant interaction between low vitamin K1 and antihypertension medication use was detected (P = 0.016). Hypertension medication users with low serum vitamin K1 were more likely to have extreme CAC progression than were medication users without extreme CAC progression [OR (95% CI): 2.37 (1.38, 4.09)]. In replication, baseline antihypertensive medication users in the supplementation group had less CAC progression than did those in the control group [adjusted mean ± SEM of the 3-y CAC change was +5 ± 20 Agatston units (AU) in the vitamin K1 group (n = 40) and +44 ± 13 AU in the placebo group (n = 49); P < 0.01]. Although the point estimate of our primary analysis suggests low serum vitamin K1 is associated with greater CAC progression, the difference was NS. Low serum vitamin K1 was significantly associated with CAC progression in antihypertension medication users, which, to our knowledge, is a novel finding conditionally replicated by using an independent sample. Intervention trials are needed to determine whether improving serum vitamin K1 reduces CAC progression, especially in hypertensive individuals. This trial was registered at clinicaltrials.gov as NCT00183001.

Influence of dietary weight‐loss on vitamins D and K in obese post‐menopausal women

Obese persons are at risk for fat‐soluble vitamin (FSV) insufficiency. It is also plausible that weight loss is associated with change in FSV status. Hence, our aim was to examine associations between change in weight status and change in vitamin D and K status in 89 post‐menopausal obese women (mean±SD BMI=33.1±3.6kg/m2, age=58±6y), following a hypocaloric weight‐loss program. All women received 200IU/d vitamin D3 and 80 mcg/d vitamin K1. On average, baseline serum 25‐hydroxyvitamin‐D (25(OH)D) and vitamin K1 concentrations were within normal ranges (51±18nmol/L, 1.3±1.0nmol/L respectively). After 20‐weeks, women lost 11.1±5.3% of initial body weight and 8.0±3.2kg of fat mass. 25(OH)D increased by 10±14nmol/L (p&lt;0.01, season‐adjusted), but serum vitamin K1 did not change (p=0.85, triglyceride‐adjusted). Using linear models, with change in FSV status as outcomes and change in weight‐status as primary exposures in separate analyses, there was no association between change in 25(OH)D and change in weight, BMI, or fat mass [unstd B(p‐value)= −0.51(0.15), −0.98(0.32), −0.60(0.19) respectively] or between change in serum K1 and change in weight, BMI, or fat mass [unstd B(p‐value)= −0.04(0.17), −0.10(0.16), −0.06(0.10) respectively]. Our data do not suggest moderate weight loss is associated with change in serum measures of vitamin D or K. Supported by NIA R01AGDK20583, P30AG21332 &amp; USDA ARS #58‐1950‐7707.

Vitamin K supplementation in postmenopausal women with osteopenia (ECKO trial): a randomized controlled trial.

BackgroundVitamin K has been widely promoted as a supplement for decreasing bone loss in postmenopausal women, but the long-term benefits and potential harms are unknown. This study was conducted to determine whether daily high-dose vitamin K1 supplementation safely reduces bone loss, bone turnover, and fractures.Methods and FindingsThis single-center study was designed as a 2-y randomized, placebo-controlled, double-blind trial, extended for earlier participants for up to an additional 2 y because of interest in long-term safety and fractures. A total of 440 postmenopausal women with osteopenia were randomized to either 5 mg of vitamin K1 or placebo daily. Primary outcomes were changes in BMD at the lumbar spine and total hip at 2 y. Secondary outcomes included changes in BMD at other sites and other time points, bone turnover markers, height, fractures, adverse effects, and health-related quality of life. This study has a power of 90% to detect 3% differences in BMD between the two groups. The women in this study were vitamin D replete, with a mean serum 25-hydroxyvitamin D level of 77 nmol/l at baseline. Over 2 y, BMD decreased by −1.28% and −1.22% (p = 0.84) (difference of −0.06%; 95% confidence interval [CI] −0.67% to 0.54%) at the lumbar spine and −0.69% and −0.88% (p = 0.51) (difference of 0.19%; 95% CI −0.37% to 0.75%) at the total hip in the vitamin K and placebo groups, respectively. There were no significant differences in changes in BMD at any site between the two groups over the 2- to 4-y period. Daily vitamin K1 supplementation increased serum vitamin K1 levels by 10-fold, and decreased the percentage of undercarboxylated osteocalcin and total osteocalcin levels (bone formation marker). However, C-telopeptide levels (bone resorption marker) were not significantly different between the two groups. Fewer women in the vitamin K group had clinical fractures (nine versus 20, p = 0.04) and fewer had cancers (three versus 12, p = 0.02). Vitamin K supplements were well-tolerated over the 4-y period. There were no significant differences in adverse effects or health-related quality of life between the two groups. The study was not powered to examine fractures or cancers, and their numbers were small.ConclusionsDaily 5 mg of vitamin K1 supplementation for 2 to 4 y does not protect against age-related decline in BMD, but may protect against fractures and cancers in postmenopausal women with osteopenia. More studies are needed to further examine the effect of vitamin K on fractures and cancers. Trial registration: ClinicalTrials.gov (#NCT00150969) and Current Controlled Trials (#ISRCTN61708241)

Vitamin K Prophylaxis for Preterm Infants: A Randomized, Controlled Trial of 3 Regimens

Preterm infants may be at particular risk from either inadequate or excessive vitamin K prophylaxis. Our goal was to assess vitamin K status and metabolism in preterm infants after 3 regimens of prophylaxis. Infants <32 weeks' gestation were randomized to receive 0.5 mg (control) or 0.2 mg of vitamin K1 intramuscularly or 0.2 mg intravenously after delivery. Primary outcome measures were serum vitamin K1, its epoxide metabolite (vitamin K1 2,3-epoxide), and undercarboxylated prothrombin assessed at birth, 5 days, and after 2 weeks of full enteral feeds. Secondary outcome measures included prothrombin time and factor II concentrations. On day 5, serum vitamin K1 concentrations in the 3 groups ranged widely (2.9-388.0 ng/mL) but were consistently higher than the adult range (0.15-1.55 ng/mL). Presence of vitamin K1 2,3-epoxide on day 5 was strongly associated with higher vitamin K1 bolus doses. Vitamin K1 2,3-epoxide was detected in 7 of 29 and 4 of 29 infants from the groups that received 0.5 mg intramuscularly and 0.2 mg intravenously, respectively, but in none of 32 infants from group that received 0.2 mg intramuscularly. After 2 weeks of full enteral feeding, serum vitamin K1 was lower in the infants who received 0.2 mg intravenously compared with the infants in the control group. Three infants from the 0.2-mg groups had undetectable serum vitamin K1 as early as the third postnatal week but without any evidence of even mild functional deficiency, as shown by their normal undercarboxylated prothrombin concentrations. Vitamin K1 prophylaxis with 0.2 mg administered intramuscularly maintained adequate vitamin K status of preterm infants until a median age of 25 postnatal days and did not cause early vitamin K1 2,3-epoxide accumulation. In contrast, 0.2 mg administered intravenously and 0.5 mg administered intramuscularly led to vitamin K1 2,3-epoxide accumulation, possibly indicating overload of the immature liver. To protect against late vitamin K1 deficiency bleeding, breastfed preterm infants given a 0.2-mg dose of prophylaxis should receive additional supplementation when feeding has been established.

Vitamin K Status Among Children With Cystic Fibrosis and Its Relationship to Bone Mineral Density and Bone Turnover

The aim of this study was to assess vitamin K status in an unselected population of children with cystic fibrosis (CF) and to investigate any vitamin K effect on bone turnover and bone mineral status. Children > or =5 years of age who were attending the CF unit were invited to enter the study. Fasting blood samples were analyzed for levels of vitamin K1 and prothrombin produced in vitamin K absence; total, undercarboxylated, and carboxylated osteocalcin (OC); and bone-specific alkaline phosphatase and procollagen I carboxy-terminal propeptide (bone formation markers). Levels of N-telopeptide and free pyridinoline and deoxypyridinoline (bone breakdown products) were measured in urine samples. Bone mineral density and bone mineral content were measured at the lumbar spine and for the total body with a GE Lunar Prodigy densitometer. Statistical analyses were performed with Minitab version 9.1. One hundred six children entered the study. Sixty-five of 93 children (70%) from whom blood samples were obtained showed suboptimal vitamin K status, on the basis of low serum vitamin K1 levels, increased prothrombin produced in vitamin K absence levels, or both abnormalities. Vitamin K1 levels showed a significant negative correlation with undercarboxylated OC levels but showed no significant correlation with any marker of bone turnover or measurement of bone mineral status. Undercarboxylated OC levels were correlated significantly with bone turnover markers, which themselves showed a significant negative correlation with measurements of bone mineral density and content. There were no significant correlations between carboxylated or undercarboxylated OC levels and bone density measurements. Vitamin K1 deficiency is common among children with CF, and routine supplements should be considered. Through its role in the carboxylation of OC, vitamin K deficiency may be associated with an uncoupling of the balance between bone resorption and bone formation. A cause-effect relationship between vitamin K deficiency and low bone mass has not been proved.